ESPE Abstracts (2016) 86 P-P1-618

Design and Clinical Development of TransCon Growth Hormone for Growth Hormone Deficiency (GHD)

Michael Beckerta, David Gilfoylea, Jan Møller Mikkelsenb, Grethe Rasmussena, Harald Rauc & Kennett Sprogøeb

aAscendis Pharma A/S, Hellerup, Denmark; bAscendis Pharma, Inc., Palo Alto, USA; cAscendis Pharma GmbH, Heidelberg, Germany

Background: TransCon GH is designed as a once-weekly sustained-release prodrug of recombinant human GH (hGH, somatropin). Based on the inert TransCon prodrug technology unmodified native hGH is released with a Cmax and AUC comparable to daily therapy. TransCon GH leverages the known pharmacology of daily hGH and is being developed for the treatment of GH deficiency (GHD) in children and adults.

Objective and hypotheses: Develop a safe and efficacious sustained-release hGH resulting in both hGH and IGF-I serum concentrations within the therapeutic range, leveraging the safety, efficacy, tolerability and immunogenicity of daily hGH, which have been established over decades of use.

Method: Within the TransCon GH development program a Healthy Volunteer (HV) Phase 1 and two Phase 2 studies in adults and children with GHD were conducted. Daily hGH as comparator was included in those clinical trials to enable comparison of hGH, IGF-I levels and predict auxology in the Phase 2 paediatric trial.

Results: TransCon GH was shown in HVs and GHD adults and children to be safe and well tolerated; generate predictable and dose dependent serum peak levels and overall exposure (AUC) within the therapeutic range of both GH and IGF-I, and in children to provide comparable height velocity to daily hGH. Immunogenicity was low and comparable to daily hGH, and no neutralizing antibodies have been observed.

Conclusion: To date, TransCon GH has demonstrated efficacy and safety comparable to that observed with daily hGH. Injection site reactions were generally mild and similar to daily hGH injections, with no nodule formation or lipoatrophy noted. The completed clinical studies supports Phase 3 development.

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